Mechanisms of hepatocyte growth factor activation in cancer tissues.
Mechanisms of hepatocyte growth factor activation in cancer tissues.
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DOI：
10.3390/cancers6041890
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发表时间：
2014-09-29
期刊：
影响因子：
5.2
通讯作者：
Kataoka H
中科院分区：
文献类型：
--
作者：
Kawaguchi M;Kataoka H
肝细胞生长因子/分散因子（HGF/SF）通过其特异性受体MET在癌症进展中起关键作用。HGF/SF通常由基质细胞如成纤维细胞合成和分泌为无活性前体（pro-HGF/SF）。据报道，几种丝氨酸蛋白酶将pro-HGF/SF转化为成熟HGF/SF，其中HGF激活剂（HGFA）和间质蛋白酶是最有效的激活剂。已在各种癌症中观察到两种蛋白酶的活性增加。HGFA主要由肝脏合成，并作为无活性前体形式分泌。在癌组织中，pro-HGFA可能被凝血酶和/或人激肽释放酶1相关肽酶（KLK）-4和KLK-5激活。间质蛋白酶是一种II型跨膜丝氨酸蛋白酶，由大多数上皮细胞表达，也作为无活性的酶原合成。间质蛋白酶激活可能由自激活或其他胰蛋白酶样蛋白酶介导。最近的研究表明，间质蛋白酶自激活是由酸性环境促进的。考虑到实体瘤的温和酸性细胞外环境，间质蛋白酶活化因此可以在肿瘤微环境中加速。HGFA和间质蛋白酶活性在细胞周围微环境中由HGFA抑制剂（HAI）-1（HAI-1）和/或HAI-2调节。HAI可能通过调节HGF/SF激活蛋白酶在癌细胞生物学中发挥重要作用。
Hepatocyte growth factor/scatter factor (HGF/SF) plays critical roles in cancer progression through its specific receptor, MET. HGF/SF is usually synthesized and secreted as an inactive proform (pro-HGF/SF) by stromal cells, such as fibroblasts. Several serine proteases are reported to convert pro-HGF/SF to mature HGF/SF and among these, HGF activator (HGFA) and matriptase are the most potent activators. Increased activities of both proteases have been observed in various cancers. HGFA is synthesized mainly by the liver and secreted as an inactive pro-form. In cancer tissues, pro-HGFA is likely activated by thrombin and/or human kallikrein 1-related peptidase (KLK)-4 and KLK-5. Matriptase is a type II transmembrane serine protease that is expressed by most epithelial cells and is also synthesized as an inactive zymogen. Matriptase activation is likely to be mediated by autoactivation or by other trypsin-like proteases. Recent studies revealed that matriptase autoactivation is promoted by an acidic environment. Given the mildly acidic extracellular environment of solid tumors, matriptase activation may, thus, be accelerated in the tumor microenvironment. HGFA and matriptase activities are regulated by HGFA inhibitor (HAI)-1 (HAI-1) and/or HAI-2 in the pericellular microenvironment. HAIs may have an important role in cancer cell biology by regulating HGF/SF-activating proteases.
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DOI：
10.1073/pnas.89.23.11574
发表时间：
1992-12-01
影响因子：
11.1
作者：
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发表时间：
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影响因子：
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DOI：
10.1006/bbrc.1999.0268
发表时间：
1999-02-24
影响因子：
3.1
作者：
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